Signs Of Central Sensitization Research Articles

Migraine and psychosomatic comorbidity

As a common neurological disorder (10-15% of the population), migraine is associated with numerous comorbidities, particularly other pain syndromes, mental illnesses and functional disorders. These 'psychosomatic' comorbidities increase with migraine severity. Severely affected, comorbid patients also often have a poorer response to specific migraine therapy. Interestingly, migraine and the comorbidities mentioned have a number of common aetiological or facilitating factors, e.g. genetic factors, and show a higher incidence in women and in people with previous traumatic experiences, as well as (in the case of pain syndromes) signs of central sensitization. Another common feature is the association with current or chronic stress. We propose an extended diathesis-stress model that takes into account interrelated but individually different vulnerabilities and, depending on the stress experience, can depict both the occurrence of individual disorders (e.g. an isolated migraine) and the joint occurrence of migraine with other pain syndromes and other psychosomatic comorbidities. In summary, psychosomatic comorbidities should always be kept in mind in migraine therapy and, if necessary, treated early and multimodally.

Association between central sensitization, pain sensitivity and balance control in patients with migraine.

Balance alterations are prevalent among pain conditions, including migraine. The mechanisms explaining the association between pain and balance are unclear, as well as whether levels of pain sensitivity correlate with impaired balance. Our aim was therefore to investigate the association between balance, central sensitization symptoms and pain sensitivity in patients with migraine. This cross-sectional study included 50 patients and demographic, clinical information, central sensitization inventory (CSI) and pain catastrophizing (PCS) scores were obtained. Patients underwent a standardized protocol evaluating balance and pain thresholds for cold (CPT), heat (HPT), mechanical (MPT) and pressure (PPT) in trigeminal (V1) and extra-trigeminal (C6) dermatomes. Data were analysed using Person's correlation, linear regression models and contrasting the presence and absence of central sensitization symptoms through T-tests. Mild-to-moderate correlations were observed between balance and MPT in V1 (r = -0.24, p = 0.046) and C6 (r = -0.41, p = 0.002), CPT in V1 (r = 0.31, p = 0.026), CSI scores (r = 0.27, p = 0.029) and migraine frequency (r = 0.25, p = 0.040). Balance was explained by CPT and MPT (R2 = 0.32, p = 0.001). The variance of CSI was explained by PCS scores and balance (R2 = 0.28, p = 0.001). Patients with symptoms of central sensitization presented an increased balance impairment (p = 0.044) and higher catastrophizing levels (p = 0.001) in contrast to patients without symptoms. Balance impairment is associated with reduced pain thresholds and higher CSI scores. These results may help to elucidate the aetiology of balance alterations among chronic pain conditions. For the first time, it has been shown that balance alterations can reflect greater pain sensitivity and signs of central sensitization in patients with migraine. This opens up perspectives for future studies to understand the mechanisms and further factors associated with balance and pain sensitivity in migraine.

Features of clinical manifestations of rheumatoid arthritis in patients after failure of conventional synthetic disease-modifying antirheumatic drugs therapy depending on the signs of central sensitization

Central sensitization (CS) is a condition characterised by (associated with) neuroplastic changes in nociceptive neurons, sub-threshold afferent input, pain hypersensitivity and development widespread pain. Insufficient response to disease-modifying antirheumatic drugs (DMARDs) can be caused by CS.Objective – to evaluate the features of clinical manifestations of RA in patients with ineffective antirheumatic therapy, depending on the presence of signs of CS.Material and methods. The study group included 509 patients diagnosed with RA (according to ACR/EULAR classification criteria, 2010) with moderate or high disease activity (DAS28-CRP≥3.2) and ineffectiveness or intolerance of conventional synthetic DMARDs, biological DMARDs and JAK inhibitors. Disease activity in patient with RA was assessed by DAS28-CRP. Our study did not include an examination by a neurologist to detect signs of CS, so the Central Sensitization Inventory (CSI) (part one) was used. The BPI questionnaire was used for assessing clinical pain intensity. The PainDETECT, FSS, FIRST, HAQ questionnaires were used for screening neuropathic pain symptoms (NPS), fatigue, fibromyalgia signs and functional impairment, respectively. The HADS questionnaire was recommended for early diagnosis anxiety and depression disorders.Results. Signs of CS (CSI≥40), with a median of 42 [32; 53], were found in 57.2% of the examined patient. Patients with signs of CS were established to have poorer health measure (PGA – 64.6±13.5 and 53.5±16.8; p=0.001), higher pain intensity in all BPI scales, longer morning stiffness – 90 [30; 180] and 60 [20; 120] minutes (p=0.001), more painful joints – 8 [5; 12] and 7 [4; 10] (p=0.005), worse functional status in HAQ (1.65±0.7 and 1.08±0.5; p=0.001) and higher disease activity in DAS28-CRP (4.9±1.0 and 4.6±0.9; p=0.001) compared to patients without signs of CS. There was also direct correlation between CS and a high frequency of having an NPS (PainDETECT>18) – 34.5% and 10.3% (p=0.001), significant anxiety and depression (HADS>11) – 29,0% and 5.1% (p=0.001) and 26.3% and 4.2% (p=0.001) respectively, fatigue (FSS) – 96.5% and 70.4% (p=0.001), signs of fibromyalgia (FIRST≥5) – 38.4% and 6.1% (p=0.001).Conclusion. The presence of signs of CS in patient with RA significantly enhance many symptoms of disease, being associated with higher pain intensity, fatigue, impaired function, higher incidence of NPS, depression and anxiety, and fibromyalgia.

Sleep quality and polysomnographic changes in patients with chronic pain with and without central sensitization signs

BackgroundInsufficient sleep is common nowadays and it can be associated with chronic pain. ObjectiveTo describe the main polysomnographic findings in patients with chronic musculoskeletal pain and to estimate the association between sleep quality, polysomnography variables and chronic musculoskeletal pain. MethodsThis cross-sectional research analyzed a database from polysomnography type 1 exams results and then collected data via an electronic form from these patients. The form collected sociodemographic data and presented clinical questionnaires for measuring sleep quality, sleepiness, pain intensity and central sensitization signs. Pearson's correlation coefficient and odds ratio were used to estimate the associations. ResultsThe mean age of the respondents was 55.1 (SD 13.4) years. The mean score of the Central Sensitization Inventory showed signs of central sensitization (50.1; SD 13.4) in the participants. Most patients (86%) had 1 or more nocturnal awakenings, 90% had one or more episodes of sleep apnea, 47% had Rapid Eye Movement sleep phase latency greater than 70–120 min and the mean sleep efficiency among all participants was 81.6%. The Pittsburgh Sleep Quality Index score was correlated with the CSI score (r = 0.55; 95% CI: 0.45, 0.61). People with central sensitization signs have 2.6 times more chance to present sleep episodes of blood oxygen saturation below 90% (OR = 2.62; 95% CI:1.23, 6.47). ConclusionMost people with central sensitization signs had poor sleep quality, night waking episodes and specific disturbances in sleep phases. The findings showed association between central sensitization, sleep quality, nocturnal awakening, and changes in blood oxygen saturation during sleep.

Signs of Nervous System Sensitization in Female Runners with Chronic Patellofemoral Pain.

Patellofemoral pain (PFP) is a common overuse injury among runners, affecting females at a higher rate than males. PFP can often become chronic, with evidence suggesting it may be linked to both peripheral and central sensitization of the nervous system. Sensitization of the nervous system can be identified through quantitative sensory testing (QST). The primary objective of this pilot study was to quantify and compare pain sensitivity as identified through QST measures, in active female runners with and without PFP. Cohort Study. Twenty healthy female runners and 17 female runners with chronic PFP symptoms were enrolled. Subjects completed the Knee injury and Osteoarthritis Outcome Score for Patellofemoral Pain (KOOS-PF), University of Wisconsin Running Injury and Recovery Index (UWRI), and the Brief Pain Inventory (BPI). QST consisted of pressure pain threshold testing to three local and three distant sites to the knee, heat temporal summation, heat pain threshold, and conditioned pain modulation. Data was analyzed utilizing independent t-tests for comparison of between-group data, effect sizes for QST measures (Pearson's r), and Pearson's correlation coefficient between pressure pain threshold values at the knee and functional testing. The PFP group exhibited significantly lower scores on the KOOS-PF (p<0.001), BPI Pain Severity and Interference Scores (p<0.001), and UWRI (p<0.001). Primary hyperalgesia, identified through decreased pressure pain threshold at the knee, was detected in the PFP group at the central patella (p<0.001), lateral patellar retinaculum (p=0.003), and patellar tendon (p=0.006). Secondary hyperalgesia, a sign of central sensitization, was observed via differences in pressure pain threshold testing for the PFP group at the uninvolved knee (p=0.012 to p=0.042), involved extremity remote sites (p=0.001 to p=0.006), and uninvolved extremity remote sites (p=0.013 to p=0.021). Compared to healthy controls, female runners with chronic PFP symptoms exhibit signs of both peripheral sensitization. Despite actively participating in running, nervous system sensitization may contribute to continued pain in these individuals. For female runners with chronic PFP, physical therapy management may need to include interventions which address signs of central and peripheral sensitization. Level 3.

Myofascial Trigger Points and Central Sensitization Signs, but No Anxiety, Are Shown in Women with Dysmenorrhea: A Case-Control Study.

This study was designed following an observational, cross-sectional, case-control model. A total sample of 80 subjects was recruited trough social webs and advertising (PD n = 39) (CG n = 41). PPT in RA and AT was assessed bilaterally through algometry, and anxiety was evaluated through the State-Trait Anxiety Inventory. Statistically significant differences (p &lt; 0.001) were shown for NRS average and maximum increase, as well as lower bilaterally RA and TA PPT in favor of PD group compared to CG. State or trait STAI did not show any statistically significant differences (p &gt; 0.05) between groups. In this study, women with PD reported symptoms of myofascial pain syndrome and central sensitization, when compared with healthy controls, without any sign of anxiety acting as a confounder for pain sensitivity.

Sensitivity to movement-evoked pain, central sensitivity symptoms, and pro-nociceptive profiles in people with chronic shoulder pain: Aparallel-group cross-sectional investigation.

To investigate whether sensitivity to movement-evoked pain (SMEP), central sensitivity symptom burden, and quantitative sensory testing (QST) outcomes differ between healthy controls and people with chronic shoulder pain. People with chronic shoulder pain (n=39) and healthy controls (n=26) completed validated questionnaires measuring demographic, pain characteristics, psychological factors, social support, sleep quality, central sensitivity inventory (CSI), and physical activity levels. A blinded assessor administered QST measuring pressure pain threshold, temporal summation, conditioned pain modulation, and cold hyperalgesia. All participants performed repeated lifting of weighted canisters and reported severity of pain over successive lifts of the weighted canisters. Between-group differences in the QST, SMEP and CSI scores were investigated. Demographic and psychosocial variables were adjusted in the analyses. Dynamic mechanical allodynia, mechanical temporal summation, movement-evoked pain scores, SMEP index, and CSI scores were significantly (p ≤ 0.05) higher in the chronic shoulder pain group than in healthy controls. A significant proportion of people with chronic shoulder pain presented with pro-nociceptive profiles and experienced higher pain severity, interference, and disability. People with chronic shoulder pain displayed symptoms and signs of central sensitization. Future research should investigate the predictive role of central sensitization on clinical outcomes in shoulder pain.

Modulation of the N13 component of the somatosensory evoked potentials in an experimental model of central sensitization in humans

The N13 component of somatosensory evoked potential (N13 SEP) represents the segmental response of dorsal horn neurons. In this neurophysiological study, we aimed to verify whether N13 SEP might reflect excitability changes of dorsal horn neurons during central sensitization. In 22 healthy participants, we investigated how central sensitization induced by application of topical capsaicin to the ulnar nerve territory of the hand dorsum modulated N13 SEP elicited by ulnar nerve stimulation. Using a double-blind placebo-controlled crossover design, we also tested whether pregabalin, an analgesic drug with proven efficacy on the dorsal horn, influenced capsaicin-induced N13 SEP modulation. Topical application of capsaicin produced an area of secondary mechanical hyperalgesia, a sign of central sensitization, and increased the N13 SEP amplitude but not the peripheral N9 nor the cortical N20-P25 amplitude. This increase in N13 SEP amplitude paralleled the mechanical hyperalgesia and persisted for 120 min. Pregabalin prevented the N13 SEP modulation associated with capsaicin-induced central sensitization, whereas capsaicin application still increased N13 SEP amplitude in the placebo treatment session. Our neurophysiological study showed that capsaicin application specifically modulates N13 SEP and that this modulation is prevented by pregabalin, thus suggesting that N13 SEP may reflect changes in dorsal horn excitability and represent a useful biomarker of central sensitization in human studies.

Central sensitization of dorsal root potentials and dorsal root reflexes: An in vitro study in the mouse spinal cord.

Axo-axonic contacts onto central terminals of primary afferents modulate sensory inputs to the spinal cord. These contacts produce primary afferent depolarization (PAD), which serves as a mechanism for presynaptic inhibition, and also produce dorsal root reflexes (DRRs), which may regulate the excitability of peripheral terminals and second order neurons. We aimed to identify changes in these responses as a consequence of peripheral inflammation. In vitro spinal cord recordings of spontaneous activities in dorsal and ventral roots were performed in control mice and following paw inflammation. We also used pharmacological assays to define the neurotransmitter systems implicated in such responses. Paw inflammation increased the frequency and amplitude of spontaneous dorsal root depolarizations, the occurrence of DRRs and the amplitude of ventral roots depolarizations. PAD was classified in two different patterns based on their relation to ventral activity: time-locked and independent events. Both patterns increased in amplitude after paw inflammation, and independent events also increased in frequency. The circuits that were responsible for this activity implicated both glutamatergic and GABAergic transmission. Adrenergic modulation differentially affected both types of PAD, and this modulation changed after paw inflammation. Our findings suggest the existence of independent spinal circuits at the origin of PAD and DRRs. Inflammation modulates these circuits differentially, unveiling varied mechanisms of spinal sensitization. This in vitro approach provides an isolated model for the study of the mechanisms of central sensitization and for the performance of pharmacological assays with the purpose of identifying and testing novel antinociceptive targets. Spinal circuits modulate activity of primary afferents acting on central terminals. Under in vitro conditions, dorsal roots show spontaneous activity in the form of depolarizations and action potentials. Our findings are consistent with the existence of several independent generator circuits. Experimental paw inflammation reduced mechanical withdrawal threshold and significantly increased the spontaneous activity of dorsal roots, which may be secondary to an enhanced output of spinal generators. This can be considered as a novel sign of central sensitization.

Symptom severity is associated with signs of central sensitization in patients with asthma.

Asthma is characterized by recurrent episodes of wheezing, dyspnoea, chest tightness and cough. In addition to respiratory symptoms, previous studies have reported the presence of pain. To analyse the nociceptive processing of young adults with well-controlled asthma. A cross-sectional case-control study was performed. Patients diagnosed with persistent well-controlled asthma were recruited from the 'Complejo Hospitalario Universitario' (Granada). Main outcomes included pain processing, measured by the pressure-pain thresholds (PPTs) and temporal summation and latency of pain; symptoms, including cough (Leicester Cough Questionnaire) and dyspnoea (Borg scale); and catastrophic cognitions about breathlessness, assessed by the Breathlessness Catastrophizing Scale (BCS). Seven-two participants were finally recruited in our study. Patients with asthma presented lower pressure thresholds (p < 0.05) and significant differences in latency and summation tests. These patients also presented a greater cough level, with significant differences in all subscales (p < 0.05). Significant differences were also found in the BCS between groups (p < 0.001). Our results show a decrease of PPTs and a greater pain intensity in latency and summation tests, suggesting an abnormal pain processing in patients with asthma.

AB0135 A VERY EARLY CLINICAL RESPONSE TO TOFACITINIB IS ASSOCIATED WITH LOW RHEUMATOID ARTHRITIS ACTIVITY AFTER 3 AND 6 MONTHS

Background:JAK inhibitors block intracellular signaling pathways responsible for the synthesis of cytokines and mediators involved in the development of chronic pain and central sensitization (CS). This determines a very rapid clinical response to JAK inhibitors. However, it is not clear how the significant pain reduction in the first weeks of therapy is associated with the achievement of low rheumatoid arthritis (RA) activity.Objectives:to assess the relationship between the early clinical response to tofacitinib and the decrease in RA activity after 3 and 6 months.Methods:Study group included 88 patients with RA, their age was 53±11,5, 79.3% of women, 89.8% of RF “+”, DAS28 5.2±1.2, receiving DMARDs (methotrexate 59.5% and leflunomide 19.8%), who were administered with tofacitinib 5 mg 2 times a day due to inefficacy or intolerance of biological DMARDs. There were assessed the pain severity using Brief pain inventory (BPI) questionnaire, the presence of neuropathic pain component (NPC) using PainDETECT questionnaire and signs of CS using Central Sensitisation Inventory (CSI) questionnaire at early time after tofacitinib administration, RA activity using DAS28 after 3 and 6 months.Results:The mean pain severity at baseline was 5.3±2.0 according to the visual analogue scale (VAS 0-10), 51.1% of patients had signs of central sensitization (CSI ≥ 40), 15.9% had NPC (PainDETECT ≥18). 7 days after tofacitinib intake there was statistically reliable reduction of pain severity – up to 4.1±1.8 (р&lt;0.05) and CS – CSI from 40.4±13.5 to 36.5±12.5 (р=0.01). After 28 days, the effect was higher: the pain level (VAS) was 2.8±1.6 (p=0.000), PainDETECT decreased from 11.8±5.6 to 6.8±3.1 (p=0.000), CSI – to 31.6±13.9 (p=0.000). DAS28 after 3 and 6 months was 3.7±1.3 and 3.6±1.2. The number of patients with pain decrease of ≥50% after 28 days of therapy was 59.9%. Low RA activity after 3 months. (DAS28 ≤3.2) was achieved in 64.4% of patients. There was a clear correlation between the number of patients with significant pain reduction at 28 days and the number of patients with low RA activity after 3 and 6 months (rS=0.548, p=0.000; rS=0.790, p=0.000). Six patients withdrew from the study due to inefficacy or social reasons. There were no serious adverse reactions.Conclusion:The application of JAK inhibitor tofacitinib allows to reach a fast analgesic effect and reduce CS signs. An early clinical response to tofacitinib (pain relief) predicts a decrease in RA activity after 3 and 6 months of the therapy.Limitation: Open-label observatory study.Disclosure of Interests:None declared

Protective role of natural killer cells in neuropathic pain conditions.

During the past few years, the research of chronic neuropathic pain has focused on neuroinflammation within the central nervous system and its impact on pain chronicity. As part of the ERA-Net NEURON consortium, we aimed to identify immune cell patterns in the cerebrospinal fluid (CSF) of patients with herpes zoster neuralgia and patients with polyneuropathy (PNP), which may contribute to pain chronicity in these neuropathic pain conditions. Cerebrospinal fluid of 41 patients (10 herpes zoster and 31 PNP) was analyzed by flow cytometry identifying lymphocyte subsets: CD4+ (T-helper cells), CD8+ (cytotoxic T cells), CD19+ (B cells), and CD56+ (natural killer [NK]) cells. At baseline and at follow-up, the somatosensory phenotype was assessed with quantitative sensory testing. In addition, the patients answered epidemiological questionnaires and the PainDETECT questionnaire. Immune cell profiles and somatosensory profiles, as well as painDETECT questionnaire scores, were analyzed and correlated to determine specific immune cell patterns, which contribute to chronic pain. We found a negative correlation (P = 0.004, r = -0.596) between the frequency of NK cells and mechanical pain sensitivity (MPS), one of the most relevant quantitative sensory testing markers for central sensitization; a high frequency of NK cells correlated with low MPS. The analysis of the individual follow-up showed a worsening of the pain condition if NK-cell frequency was low. Low NK-cell frequency is associated with signs of central sensitization (MPS), whereas high NK-cell frequency might prevent central sensitization. Therefore, NK cells seem to play a protective role within the neuroinflammatory cascade and may be used as a marker for pain chronicity.

The serotonin receptor 2A (HTR2A) rs6313 variant is associated with higher ongoing pain and signs of central sensitization in neuropathic pain patients.

The serotonin receptor 2A (HTR2A) has been described as an important facilitation mediator of spinal nociceptive processing leading to central sensitization (CS) in animal models of chronic pain. However, whether HTR2A single nucleotide variants (SNVs) modulate neuropathic pain states in patients has not been investigated so far. The aim of this study was to elucidate the potential association of HTR2A variants with sensory abnormalities or ongoing pain in neuropathic pain patients. At total of 240 neuropathic pain patients and 253 healthy volunteers were included. Patients were phenotypically characterized using standardized quantitative sensory testing (QST). Patients and controls were genotyped for HTR2A g.-1438G>A (rs6311) and c.102C>T (rs6313). Genotype-related differences in QST parameters were assessed considering QST profile clusters, principal somatosensory components and sex. There was an equal distribution of rs6313 and linked rs6311 between patients and controls. However, the rs6313 variant was significantly associated with a principal component of pinprick hyperalgesia and dynamic mechanical allodynia, indicating enhanced CS in patients with sensory loss (-0.34±0.15 vs. +0.31±0.11 vs., p<.001). In this cluster, the variant allele was also associated with single QST parameters of pinprick hyperalgesia (MPT, +0.64±0.18 vs. -0.34±0.23 p=.002; MPS, +0.66±0.17 vs. -0.09±0.23, p=.009) and ongoing pain was increased by 30%. The specific association of the rs6313 variant with pinprick hyperalgesia and increased levels of ongoing pain suggests that the HTR2A receptor might be an important modulator in the development of CS in neuropathic pain. This article presents new insights into serotonin receptor 2A-mediating mechanisms of central sensitization in neuropathic pain patients. The rs6313 variant allele was associated with increased mechanical pinprick sensitivity and increased levels of ongoing pain supporting a contribution of central sensitization in the genesis of ongoing pain providing a possible route for mechanism-based therapies.

Hyperalgesia and Central Sensitization in Subjects With Chronic Orofacial Pain: Analysis of Pain Thresholds and EEG Biomarkers.

Introduction: The presence of a temporomandibular disorder is one of the most frequent causes of orofacial pain (OFP). When pain continues beyond tissue healing time, it becomes chronic and may be caused, among other factors, by the sensitization of higher-order neurons. The aim of this study is to describe psychological characteristics of patients with chronic OFP, their peripheral pain threshold, and electroencephalography (EEG) recording, looking for possible signs of central sensitization (CS).Materials and methods: Twenty-four subjects with chronic OFP caused by temporomandibular disorder were evaluated using the Research Diagnostic Criteria for Temporomandibular Disorders Axis I and Axis II. Pain intensity, catastrophizing, and presence of CS were assessed through self-reported questionnaires. Pressure pain threshold (PPT) was recorded in facial and peripheral sites; EEG activity was recorded during open and closed eyes resting state and also during the pain threshold assessment. Pain thresholds and EEG recordings were compared with a cohort of pain-free age- and sex-matched healthy subjects.Results: Patients with chronic OFP showed a significant reduction in their pain threshold compared to healthy subjects in all sites assessed. Greater reduction in pain threshold was recorded in patients with more severe psychological symptoms. Decreased alpha and increased gamma activity was recorded in central and frontal regions of all subjects, although no significant differences were observed between groups.Discussion: A general reduction in PPT was recorded in people who suffer from chronic OFP. This result may be explained by sensitization of the central nervous system due to chronic pain conditions. Abnormal EEG activity was recorded during painful stimulation compared to the relaxed condition in both chronic OFP subjects and healthy controls.

PAIN SENSITIVITY IN CHRONIC ACHILLES TENDINOPATHY

Achilles tendinopathy is a common overuse injury sustained by athletes (including runners) that often becomes chronic. There is evidence that chronic musculoskeletal pain conditions exhibit signs of nervous system sensitization. The objective of this study was to compare pain sensitivity (pressure pain threshold [PPT], heat pain threshold [HPT], and heat temporal summation [HTS]) between active healthy adults with and without chronic Achilles tendinopathy in order to determine if signs of peripheral and/or central sensitization exist in chronic Achilles tendinopathy. Cohort study. Seventeen participants with chronic ( ≥ 3 months) Achilles tendinopathy (39.0 years ± 10.81) and 24 healthy controls (31.83 years ± 8.92) were included. All participants completed the Pain Catastrophizing Scale (PCS). Participants in the Achilles group also completed the Lower Extremity Functional Scale (LEFS) and the Victorian Institute of Sport Assessment-Achilles (VISA-A). Pain processing was quantified using PPT, HPT and HTS tests. There were no significant differences in PCS scores between groups. In the Achilles tendinopathy group, the mean VISA-A score was 58.5 ± 18.4; the mean LEFS was 63.7 ± 8.0. Primary hyperalgesia (decreased pain threshold at injury site) was detected in the Achilles tendinopathy group, as evidenced by lower PPT (p<0.0001) and lower HPT (p = 0.028). Mechanical secondary hyperalgesia, a sign of central sensitization, was found in the Achilles tendinopathy group at the tibialis anterior (p = 0.042) and non-involved Achilles (p = 0.025), but not at the thenar eminence (p = 0.276). The degree of HTS was not different between groups (p = 0.981). Active participants with chronic Achilles tendinopathy showed signs of both peripheral and central sensitization; however, widespread hyperalgesia into the upper extremities and elevated temporal summation were not observed. Evidence of differences in pain sensitivity lend support to the theory for a multifactorial model of tendinopathy, which consists of an impaired motor system, local tendon pathology, and changes in the pain/nociceptive system. Physical therapy management of chronic Achilles tendinopathy may need to address potential changes in the nervous system. Interventions used to treat chronic tendinopathies should be investigated for their potential to resolve peripheral and central sensitization. Therapy, level 2b.

The Extent of Pain Is Associated With Signs of Central Sensitization in Patients With Hip Osteoarthritis.

Central sensitization may be present in some patients with hip osteoarthritis (OA), often reflected as widespread pain. We examine the association between pain extent with signs of central sensitization and other clinical and psychological features in patients with hip OA. Thirty patients with hip OA were recruited for this cross-sectional observational study. Participants completed pain drawings on a digital tablet, which displayed frontal and dorsal views of the body. The pain extent (%) for each participant was determined by combining the frontal and dorsal pixels shaded and dividing by the total pixels of the body chart area. Participants completed patient-reported outcome measures to assess for signs and symptoms of central sensitization and psychosocial factors. Quantitative sensory testing including pain pressure thresholds (PPTs) and thermal pressure thresholds was performed at points anatomically local and distant from the hip. Women had significantly greater pain extent (6.71%) than men (2.65%) (z=-2.76, P<0.01). Across all participants, increased pain extent was significantly associated with higher scores on the Widespread Pain Index (r2 =0.426, P<0.05), painDETECT questionnaire (r2 =0.394, P<0.05), and Pain Catastrophizing Scale (r2 =0.413, P<0.05), and with lower PPTs at the thenar eminence (r2 =-0.410, P<0.05), vastus lateralis (r2 =-0.530, P<0.01), vastus medialis (r2 =0.363, P<0.05), and greater trochanter (r2 =-0.373, P<0.05). Greater pain extent was associated with several measures of signs and symptoms of central sensitization in patients with hip OA. These results support the utility of the pain drawing for identifying signs of central sensitization in patients with hip OA.

Widespread Pressure Pain Sensitivity over Nerve Trunk Areas in Women with Frequent Episodic Tension-Type Headache as a Sign of Central Sensitization.

Previous studies reported the presence of widespread pressure pain sensitivity in patients with tension-type headache. However, most of the studies assessed pressure pain sensitivity over muscle tissue. Our aim was to investigate the difference in pressure pain sensitivity over musculoskeletal and nerve symptomatic and distant areas between women with frequent episodic tension-type headache (FETTH) and healthy subjects. Thirty-two women with FETTH and 32 matched healthy women participated. Pressure pain threshold (PPT) was bilaterally assessed over several nerve trunks (greater occipital, median, radial, ulnar, common peroneal, tibialis posterior) and musculoskeletal structures (temporalis muscle, C5/C6 joint, tibialis anterior) by an assessor blinded to the subject's condition. A four-week headache diary was used to collect the intensity, frequency, and duration of headache. The Hospital Anxiety and Depression Scale was used to determine anxiety and depressive levels. Analysis of covariance found lower widespread and bilateral PPTs over all nerve trunks and musculoskeletal structures in women with FETTH pain (P < 0.001). No significant effect of anxiety and depressive levels on PPTs was found (all P > 0.222). PPT over the temporalis muscle was significantly negatively correlated with headache intensity. This study found widespread pressure pain hypersensitivity over both nerve trunks and musculoskeletal structures in women with FETTH, suggesting that the presence of central altered nociceptive processing is not just restricted to musculoskeletal areas, for example, muscles, but also pain evoked from directly provoking the nerve trunks by pressure. It is also possible that nerve tissue treatment could lead to a decrease in central sensitization and headache features.

Prognostic value of hypersensitivity reactions on epidural steroid injection outcomes: a phenotypic signature? A prospective cohort study

BackgroundStudies have found that diffuse pain, indicative of central sensitization, portends poor interventional outcomes. Multiple chemical sensitivities are associated with signs of central sensitization. We sought to prospectively determine whether...

Hyperalgesia and Central Sensitization Signs in Patients with Cluster Headache: A Cross-Sectional Study.

To investigate central sensitization (CS) in cluster headache (CH) and to evaluate its relationship with disease characteristics and psychological comorbidities. Cross-sectional study. Whether CS occurs in CH, as it does in other primary headaches, is a subject of debate. Few studies have evaluated the presence of CS and its relationship with psychological comorbidities in patients with CH. Twenty patients with episodic or chronic CH and 16 healthy controls were recruited. The variables evaluated included frequency, intensity and duration of headache attacks, pressure pain thresholds (PPTs) and wind-up (WU) ratios of pain bilaterally measured over trigeminal and extratrigeminal areas, and results of questionnaires regarding anxiety and depression (Hospital Anxiety and Depression Scale [HADS], Beck Depression Inventory [BDI], State-Trait Anxiety Inventory [STAI]), quality of life (Short Form-36 [SF-36]), headache impact (Headache Impact Test [HIT-6]), and allodynia (Allodynia Symptom Checklist [ASC]). PPT levels were significantly lower in the CH group compared with the healthy participants (all tested points, P < 0.001). No differences were found in WU ratios between groups. However, differences in HADS (P < 0.01), BDI (P < 0.01), STAI (P < 0.01), SF-36 (P < 0.01), HIT-6 (P < 0.001), and ASC (P < 0.01) were observed between groups. The healthy group showed a moderate negative correlation between SF-36 and BDI (rho = -0.59, P = 0.03). Likewise, the CH group showed a moderate negative correlation between frequency and BDI (rho = -0.52, P = 0.03), a strong positive correlation between duration and HADS (rho = 0.86, P < 0.01), and a moderate negative correlation between intensity and PPT over symptomatic V1 (rho = -0.66, P < 0.01) and over asymptomatic V1 (rho = -0.65, P < 0.01). The CH group also showed a moderate negative correlation between SF-36 and anxiety and depression variables. Our findings show that patients with CH have lower PPT levels at cranial and extracranial points, suggesting, as in other primary headaches, the presence of CS. We have also found a high prevalence of psychiatric comorbidities that correlate with the length and frequency of attacks. These findings highlight the importance of a multidisciplinary approach to the treatment of patients with CH.

Are Signs of Central Sensitization in Acute Low Back Pain a Precursor to Poor Outcome?

Central sensitization is considered to have a pathophysiological role in chronic low back pain (LBP). Whether individuals with increased central sensitization early in their condition are more likely to develop persistent pain or whether it increases over time is unclear. This study aimed to determine whether sensory profiles during acute LBP differ between individuals who did and did not recover by 6 months and to identify subgroups associated with outcomes. Individuals with acute LBP (<2 weeks of onset; N = 99) underwent pain threshold (heat/cold/pressure) and conditioned pain modulation testing after completing questionnaires related to pain/disability, sleep, and psychological status. Sensory measures were compared during the acute phase (baseline) and longitudinally (baseline/6 months) between unrecovered (greater or unchanged pain and disability), partially recovered (improved but not recovered pain and/or disability), and recovered (no pain and disability) participants at 6 months. We assessed baseline patterns of sensory sensitivity alone, and with psychological and sleep data, using hierarchical clustering and related the clusters to outcome (pain/disability) at 3 and 6 months. No sensory measure at either time point differed between groups. Two subgroups were identified that associated with more (“high sensitivity”) or less (“high sensitivity and negative psychological state”) recovery. These data seem to suggest that central sensitization during the acute phase resolves for many patients, but is a precursor to the transition to chronicity when combined with other psychological features. PerspectiveCentral sensitization signs during early acute LBP does not necessarily precede poor outcome, but may be sustained in conjunction with other psychological factors and facilitate pain persistence.